GABA.sub.A receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1

Controlling the number of functional [gamma]-aminobutyric acid A (GABA.sub.A) receptors in neuronal membranes is a crucial factor for the efficacy of inhibitory neurotransmission. Here we describe the direct interaction of GABA.sub.A receptors with the ubiquitin-like protein Plic-1. Furthermore, Plic-1 is enriched at inhibitory synapses and is associated with subsynaptic membranes. Functionally, Plic-1 facilitates GABA.sub.A receptor cell surface expression without affecting the rate of receptor internalization. Plic-1 also enhances the stability of intracellular GABA.sub.A receptor subunits, increasing the number of receptors available for insertion into the plasma membrane. Our study identifies a previously unknown role for Plic-1, a modulation of GABA.sub.A receptor cell surface number, which suggests that Plic-1 facilitates accumulation of these receptors in dendritic membranes.